A prospective industrial health surveillance program has been coordinated by Carlo H. Tamburro, M.D., M.P.H., Division of Occupational Toxicology, U. Louisville School of Medicine for the past 20 years. This program provides a unique set of human medical data, work-exposure histories and tissue/serum samples suitable for analysis of short-and long-term biomarkers of toxic chemical exposure. The exposure of this occupational population to industrial chemicals has been continuously monitored and verified for periods of 12-40 years. In the Greater Louisville area, a large medically undeserved and economically-disadvantaged population resides adjacent to the industrial sites and their medical histories can be compared to industrial cohorts. These disadvantage residential populations can be monitored by the proposed biomarker program to assess their body burden relative to the industrial workers and their cohorts. The medical surveillance aspects of this Center will provide essential human medical data, work histories and tissue to develop correlations between the proposed short and long term-biomarkers with the actual disease processes associated with the chemical effluent of these industrial sites. The data obtained would allow more reliable causal linkages to be made or disprove with regard to the populations and validate the biomarkers sensitivity and specificity. The Theme for the U of L Center will focus on the use of biochemical, chemical, and molecular biological biomarkers to define exposure in human populations and to assess in these subjects subsequent health risk requiring preventive and therapeutic modalities. Five Pilot Projects have been selected which would focus on the health surveillance of industrial and residential populations in Louisville exposures to acrylonitrile, vinyl chloride, and a variety of metal catalysts of known toxicological importance. Project 1 (Tamburro/Looney) involves collection, storage, and analysis of medical data & exposure histories and collection of human tissue samples to be analyzed in the biomarker program of the following Projects. Project 2 (Benz/Nerland) will study metabolism of acrylonitrile and vinyl chloride in rat and human hepatocytes. Project 3 (Hurst/Myers) will evaluated biomarkers of intermediate duration of exposure involving hemoglobin and DNA adducts of acrylonitrile. Project 4 (Brennan/Prough) will evaluated short and potentially intermediate-term markers of acrylonitrile, vinyl chloride, and metal catalyst exposure, namely induction and persistence of expression of several enzymes of foreign compound metabolism. Project 5 (Geoghegan/Myers/Wong) will evaluated a long term biomarker, namely mutation of p53 tumor suppressor gene known to be associated with angiosarcomas derived from acrylonitrile exposure in humans.